Na plus, K ions-ATPase, an enzyme of the plasma membrane, is involved in the regulation of the internal ionic environment of most mammalian cells. Our previous work on the interactions of short-chain alkylmercury compounds, such as methylmercury and ethylmercury, with this enzyme has shown that (a) these mercurials inhibit the Na plus K ions-dependent ATPase activity of the enzyme without inhibiting its partial reactions; and (b) these unique effects of the mercurials are due to the disruption of the quaternary structure of the enzyme. The specific aim of this proposal is to utilize the mercurials as tools for the study of the quaternary structure of the enzyme, and the relation of this to the enzyme's function. Experiments will be done (a) on the kinetics of the reactions catalyzed by the mercurial-modified enzyme, and on the kinetics of ligand binding to the enzyme, in order to determine the nature of the intersubunit and intersite interactions; (b) to attempt the solubilization of the mercurial-modified enzyme in order to purify and characterize the enzyme's protomers; (c) to determine the number of catalytic subunits of the native enzyme, and whether all subunits are identical or not, through cross-linking experiments on the native and the mercurial-modified enzyme; and (d) to establish the relation of enzyme's subunit composition to its transport function by measuring Na plus, K ions-fluxes in resealed red cell membranes in which some of the enzyme subunits have been cross-linked. The long-range goals of this project are: 1. Understanding of the mechanism of the active transports of Na plus and K ions across the cell membrane. 2. Elucidation of the mechanisms of molecular and cellular effects of a group of environmental hazards; namely, the short-chain alkylmercury compounds.